PPARγ as a therapeutic target to rescue mitochondrial function in neurological disease

There is increasing evidence for the involvement of mitochondrial dysfunction and oxidative stress in the pathogenesis of many of the major neurodegenerative and neuroinflammatory diseases, suggesting that mitochondrial and antioxidant pathways may represent potential novel therapeutic targets. Recent years have seen a rapidly growing interest in the use of therapeutic strategies that can limit the defects in, or even to restore, mitochondrial function while reducing free radical generation. The peroxisome proliferation -activated receptor gamma (PPARy), a ligand-activated transcription factor, has a wide spectrum of biological functions, regulating mitochondrial function, mitochondrial turnover, energy metabolism, antioxidant defence and redox balance, immune responses and fatty acid oxidation. In this review, we explore the evidence for potential beneficial effects of PPARy agonists in a number of neurological disorders, including Parkinson's disease, Alzheimer's disease, Amyotrophic lateral sclerosis and Hunting ton's disease, ischaemia, autoimmune encephalomyelitis and neuropathic pain. We discuss the mechanisms underlying those beneficial effects in particular in relation to mitochondrial function, antioxidant defence, cell death and inflammation, and suggest that the PPARy agonists show significant promise as therapeutic agents in otherwise intractable neurological disease. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licences/by/4.0/).